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Retinoic acids and trichostatin A (TSA), a histone deacetylase inhibitor, induce human pyruvate dehydrogenase kinase 4 (PDK4) gene expression.
- Source :
-
Biochimica et biophysica acta [Biochim Biophys Acta] 2006 Mar-Apr; Vol. 1759 (3-4), pp. 141-51. Date of Electronic Publication: 2006 Apr 27. - Publication Year :
- 2006
-
Abstract
- Induction of pyruvate dehydrogenase kinase 4 (PDK4) conserves glucose and substrates for gluconeogenesis and thereby helps regulate blood glucose levels during starvation. We report here that retinoic acids (RA) as well as Trichostatin A (TSA), an inhibitor of histone deacetylase (HDAC), regulate PDK4 gene expression. Two retinoic acid response elements (RAREs) to which retinoid X receptor alpha (RXRalpha) and retinoic acid receptor alpha (RARalpha) bind and activate transcription are present in the human PDK4 (hPDK4) proximal promoter. Sp1 and CCAAT box binding factor (CBF) bind to the region between two RAREs. Mutation of either the Sp1 or the CBF site significantly decreases basal expression, transactivation by RXRalpha/RARalpha/RA, and the ability of TSA to stimulate hPDK4 gene transcription. By the chromatin immunoprecipitation assay, RA and TSA increase acetylation of histones bound to the proximal promoter as well as occupancy of CBP and Sp1. Interaction of p300/CBP with E1A completely prevented hPDK4 gene activation by RXRalpha/RARalpha/RA and TSA. The p300/CBP may enhance acetylation of histones bound to the hPDK4 promoter and cooperate with Sp1 and CBF to stimulate transcription of the hPDK4 gene in response to RA and TSA.
- Subjects :
- Acetylation
Cell Line
Histone Deacetylases metabolism
Histones metabolism
Humans
Molecular Sequence Data
Promoter Regions, Genetic genetics
Protein Binding
Protein Kinases genetics
Protein Serine-Threonine Kinases
Pyruvate Dehydrogenase Acetyl-Transferring Kinase
Receptors, Retinoic Acid genetics
Receptors, Retinoic Acid metabolism
Response Elements genetics
Retinoic Acid Receptor alpha
Retinoid X Receptor alpha genetics
Retinoid X Receptor alpha metabolism
Transcription, Genetic genetics
Transcriptional Activation
p300-CBP Transcription Factors metabolism
Enzyme Inhibitors pharmacology
Gene Expression Regulation, Enzymologic drug effects
Histone Deacetylase Inhibitors
Hydroxamic Acids pharmacology
Protein Kinases metabolism
Tretinoin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3002
- Volume :
- 1759
- Issue :
- 3-4
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta
- Publication Type :
- Academic Journal
- Accession number :
- 16757381
- Full Text :
- https://doi.org/10.1016/j.bbaexp.2006.04.005